Humans can discriminate thousands of different odorants. The human odorant receptor (OR) gene family comprises approximately 350 intact genes. Study of a small number of ORs has led to the following basic principles. First, each individual OR recognizes multiple odorants and any individual odorant activates multiple ORs. Second, a small change in concentration, or a subtle structural alteration, leads to a change in the odorant's "receptor code," suggesting how small differences may alter odor quality. However, we do not know the full combinatorial OR code for any odorant or how these codes generate different perceptual qualities. To address these questions, we will analyze the entire human OR family, using high throughput screening to test every OR against a large number of odorants. These experiments should reveal the sizes and compositions of the receptor codes for different odorants. We will look for structure-activity relationships between OR subfamilies and odorant structures. We will also explore the molecular bases for certain features of human odor perception, such as extreme sensitivity to some odorants and mixture effects.